Differential effects of anti Fas ligand and MPI on GVHD pathologies

抗 Fas 配体和 MPI 对 GVHD 病理的不同影响

• 批准号: 12557084
• 负责人: HIRANO Takao
• 金额: $ 2.62万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557084/
• 关键词: HVG; GVH; metalloproteinase inhibitor; GVL; TNF-alpha; Fas; FasL; GVHD; MPI; HVGD; IL-4; メタロプロテナーゼインヒビター

Tumor necrosis factor (TNF) and Fas ligand (FasL) have been implicated in the pathogenesis of graft-versus-host disease (GVHD), that is a major complication after allogeneic bone marrow transplantation. We here examined the ameliorating effect of a metalloproteinase inhibitor (KB-R7785) that inhibits TNF-alpha and FasL release in murine acute GVHD model after bone marrow transplantation. Administration of KB-R7785 into irradiated (BALB/c x C57BL/6) Fl mice that received C57BL/6 bone marrow cells and spleen cells reduced the mortality and weight loss in association with minimal signs of GVHD pathology in the liver, intestine, and hematopoietic tissues. The KB-R7785 treatment did not affect the hematopoietic reconstitution by donor cells. Therefore, KB-R7785 could be a potent therapeutic agent for GVHD after bone marrow transplantation

肿瘤坏死因子（TNF）和Fas配体（FasL）与移植物抗宿主病（GVHD）的发病机制有关，GVHD是同种异体骨髓移植后的主要并发症。我们在此研究了一种金属蛋白酶抑制剂（KB-R7785）在骨髓移植后小鼠急性GVHD模型中抑制tnf - α和FasL释放的改善作用。将KB-R7785注射到接受C57BL/6骨髓细胞和脾脏细胞照射的（BALB/c x C57BL/6） Fl小鼠中，降低了死亡率和体重减轻，并伴有肝脏、肠道和造血组织中GVHD病理的最小迹象。KB-R7785治疗不影响供体细胞的造血重建。因此，KB-R7785可能是骨髓移植后GVHD的有效治疗药物

项目成果

Sakurai, J. et al.: "Blockade of CTLA-4 signals inhibits Th2-mediated murine chronic graft versus host disease by an enhanced expansion of regulatory CD8 T cells"J. Immunol.. 164;2. 664-669 (2000)

Sakurai, J. 等人：“阻断 CTLA-4 信号可通过增强调节性 CD8 T 细胞的扩增来抑制 Th2 介导的小鼠慢性移植物抗宿主病”。

K,Nozawa, J,Ohata, J,Sakurai, H,Hashimoto, H,Miyajima, H,Yagita, K,Okumura, M,Azuma: "Preferential blockade of CD8(+) T cell responses by administration of anti-CD137 ligand monoclonal antibody results in differential effect on development of murine acute

K,Nozawa, J,Ohata, J,Sakurai, H,Hashimoto, H,Miyajima, H,Yagita, K,Okumura, M,Azuma：“通过施用抗 CD137 配体单克隆抗体优先阻断 CD8( ) T 细胞反应

Sakurai, J. et al.: "Blockade of CTLA-4 signals inhibits Th2-mediated murine chronic graft versus host disease by an enhanced expansion of regulatory CD8 T cells."J. Immunol.. 164;2. 664-669 (2000)

Sakurai, J. 等人：“阻断 CTLA-4 信号可通过增强调节性 CD8 T 细胞的扩增来抑制 Th2 介导的小鼠慢性移植物抗宿主病。”

Nozawa, K. et al.: "Preferential Blockade of CD8+ T Cell responses by administration of anti-CD137 ligand monoclonal antibody results in differential effect on development of murine acute and chronic graft-versus-host diseases."J. Immunol.. 167;9. 4981-49

Nozawa, K. 等人：“通过施用抗 CD137 配体单克隆抗体优先阻断 CD8 T 细胞反应，对小鼠急性和慢性移植物抗宿主疾病的发展产生不同的影响。”

J,Sakurai, J,Ohata, K,Saito, H,Miyajima, T,Hirano, T,Kohsaka, S,Enomoto, K,Okumura, M,Azuma: "Blockade of CTLA-4 signals inhibits Th2-mediatei murine chronic graft versus host disease by an enhanced expansion of regulatory CD8 T cells."J. Immunol. 164. 66

J,Sakurai, J,Ohata, K,Saito, H,Miyajima, T,Hirano, T,Kohsaka, S,Enomoto, K,Okumura, M,Azuma：“阻断 CTLA-4 信号可抑制 Th2 介导的小鼠慢性移植物